CN102899413A - Application of single nucleotide polymorphisms of rs2735591 in detection of leprosy susceptibility genes - Google Patents
Application of single nucleotide polymorphisms of rs2735591 in detection of leprosy susceptibility genes Download PDFInfo
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Abstract
The invention discloses an application of single nucleotide polymorphisms of rs2735591 in detection of leprosy susceptibility genes. A technical scheme protected by the application is to detect the application of rs2735591 polymorphisms or genotypic substances in human genomes in the preparation of products for detecting single nucleotide polymorphisms relevant to leprosy. Substances for detecting rs2735591 polymorphisms and other substances (such as other substances for detecting single nucleotide polymorphisms relevant to the leprosy) can be integrated to prepare products for screening leprosy patients.
Description
Technical field
The present invention relates to the application of single nucleotide polymorphism rs2735591 in detecting the leprosy tumor susceptibility gene.
Background technology
Single nucleotide polymorphism (single nucleotide polymorphism, SNP) refers to the variation of genome single core thuja acid, and it is the most small variation unit, is to displacement, transversion, insertion or lack formed variant form by the single core thuja acid.Single nucleotide polymorphism is highdensity genetic marker on the genome, and the SNP quantity of having found in human genome surpasses 30,000,000.As third generation genetic marker SNP One's name is legion, densely distributed, be easy to detect, thereby be desirable gene type target.The SNP somatotype detects at disease genome (such as disease susceptibility), is significant in the researchs such as Drug Discovery (drug effect, drug metabolism difference and untoward reaction) and Swarm Evolution.
At present existing several different methods can be used for SNP and detects, such as dna sequencing, Restriction fragment length polymorphism, single strand conformation polymorphism, sex change high performance liquid chromatography, SNP chip.Wherein, the SNP chip comprises chip based on nucleic acid hybridization reaction, based on the chip of single base extension, based on the chip of allele-specific primers extension, based on the chip of " single stage method " reaction, based on the chip of the chip of primer ligation, the reaction of constraint based restriction endonuclease, based on the chip of protein D NA association reaction, and based on the chip (Zhang Xiaoyan etc. of fluorescence molecule DNA association reaction.With genechip detection single nucleotide polymorphism reaction principle.Chinese biological engineering magazine.2005,25(11):52～56）。
Leprosy is a kind of chronic infectious disease due to being infected by Mycobacterium leprae, and this remains a serious health problem in developing country, and annual global new cases number is 250000.Main infringement skin and peripheral nerve, and cause the nerve function lesion of non-reversibility and chronic teratogenesis to be disabled.This has been proved to be in the in the groove environmental factors of leprosy and host genetic factor and has played vital effect, estimates that inherited genetic factors is up to 57%.
The scheme of the World Health Organization is divided into tuberculosis type and knurl type to the clinical manifestation of leprosy, and respectively corresponding Th1(is cell-mediated) and Th2(body fluid mediate) immunne response of the human body of tissue.The multifarious clinical manifestation of leprosy reflects human body to two kinds of distinct immunne responses of allogenic disease substance, and this just illustrates the importance of genetic predisposition in the leprosy morbidity.The result of genetic research shows that heredity is all relevant with the disease progression of vulnerability to leprosy and its clinical subtype.
Summary of the invention
Technical problem to be solved by this invention provides the new purposes of single nucleotide polymorphism rs2735591 aspect leprosy.
New purposes provided by the present invention is following 1)-9) at least a:
1) polymorphism of rs2735591 or the application of genotypic material in the product of the preparation detection single nucleotide polymorphism relevant with leprosy in the detection human genome;
2) detect the application in the product of characterization or the assistant identification single nucleotide polymorphism relevant with leprosy of the polymorphism of rs2735591 in the human genome or genotypic material;
3) polymorphism of rs2735591 or the genotypic material application in preparation examination leper product in the detection human genome;
4) polymorphism of rs2735591 or the genotypic material application in preparation detection leprosy susceptibility product in the detection human genome;
5) application of the single nucleotide polymorphism in the human genome in the product of preparation detection leprosy tumor susceptibility gene, wherein, described single nucleotide polymorphism is that refSNP ID is the dna sequence polymorphism of rs2735591;
6) application of the single nucleotide polymorphism in the human genome in the product of characterization or assistant identification leprosy tumor susceptibility gene, wherein, described single nucleotide polymorphism is that refSNP ID is the dna sequence polymorphism of rs2735591;
7) application of the polymorphism of rs2735591 in preparation examination leper product in the human genome;
8) application of the polymorphism of rs2735591 in preparation detection leprosy susceptibility product in the human genome;
9) comprise the product that detects the material of rs2735591 polymorphism in the human genome, be any product in a)-d):
The product of the single nucleotide polymorphism that a) detection is relevant with leprosy,
The product of the single nucleotide polymorphism that b) evaluation or assistant identification are relevant with leprosy,
C) examination leper product,
D) detect leprosy susceptibility product.
In an embodiment of the present invention, described leprosy is specially the Chinese han population leprosy.
Rs2735591 is the SNP site of two equipotential polymorphisms on the human chromosome 1p 22, and this variation is conversion (C/T then is G/A on its complementary strand).Described rs2735591 genotype is CC, CT or TT.Described CC is that the rs2735591 site is the homozygous of C, and described TT is that the rs2735591 site is the homozygous of T, and described CT is that the rs2735591 site is the heterozygous of T and C.The polymorphism of rs2735591 or genotype specifically can be the Nucleotide kind that detects rs2735591 in the described detection human genome.
The P value that experiment showed, the case-control colony that rs2735591 forms in the case colony that is comprised of 3148 lepers with by 7843 normal peoples is 1.03 * 10
-9, relative risk is 1.24, illustrates that rs2735591 is the single nucleotide polymorphism relevant with leprosy.BCL10 apart from rs2735591 2kb the experiment proved that it is a kind of new leprosy tumor susceptibility gene, also finds in addition two candidates' tumor susceptibility gene at the desmic region of rs2735591: C1orf52 and DDAH1.C1orf52 adjoins mutually with DDAH1 and BCL10.
Experiment showed, that in three genotype of rs2735591, the ratio of the genotypic individuality of CC in normal people colony is 49.2%, the ratio 39.9% in the leper colony.In actual applications, material and other material (as detecting other the material of relevant single nucleotide polymorphism with the leprosy) gang that detects the polymorphism of rs2735591 can be prepared examination leper's product.
Wherein, the material of the polymorphism of rs2735591 can be required reagent and/or the instrument of polymorphism of determining rs2735591 by following at least a method in the detection human genome: dna sequencing, Restriction fragment length polymorphism, single strand conformation polymorphism, sex change high performance liquid chromatography and SNP chip.Wherein, the SNP chip comprises chip based on nucleic acid hybridization reaction, based on the chip of single base extension, based on the chip of allele-specific primers extension, based on the chip of " single stage method " reaction, based on the chip of the chip of primer ligation, the reaction of constraint based restriction endonuclease, based on the chip of protein D NA association reaction, and based on the chip of fluorescence molecule DNA association reaction.
Described product can be reagent or test kit, also can be the combined prod of reagent or test kit and instrument, such as the combined prod that is formed by primer and DNA sequencer, and the combined prod that is formed by PCR reagent and dna sequencing reagent and DNA sequencer.
In one embodiment of the present of invention, adopt the PCR primer amplification to comprise the genomic DNA fragment of rs2735591, take the pcr amplification product that obtains as template, adopt the single-basic extension primer to carry out single base extension, sequence to the extension products that obtains detects, and determines polymorphism and the genotype of rs2735591.Described PCR primer does not have particular requirement in sequence, as long as can amplify the genomic DNA fragment that comprises rs2735591, specifically can be the single stranded DNA shown in sequence 1 and the sequence 2.Described extension primer designs according to rs2735591 upstream in the human genome (not comprising this SNP site), front 1 Nucleotide of last 1 Nucleotide correspondence of described extension primer rs2735591 in human genome, extend as described primer and specifically can be sequence 3 in the TCCCTGTTTTATTTTTTCCTCTTAG(sequence table), certainly also can be with the above Nucleotide of upstream sequence prolongation according to rs2735591 in the human genome of the single stranded DNA shown in the sequence 3, or according to above Nucleotide of the upstream sequence of rs2735591 in human genome disappearance, as long as can make 3 ' end of this single-basic extension primer extend the Nucleotide in rs2735591 site.
The present invention is based on the GWAS data, the relation take Toll and CARD as Candidate Gene Study single nucleotide polymorphism and Chinese han population leprosy genetic predisposition finds that rs2735591 is the single nucleotide polymorphism relevant with leprosy.Material and other material (as detecting other the material of relevant single nucleotide polymorphism with the leprosy) gang that detects the polymorphism of rs2735591 can be prepared examination leper's product.
Description of drawings
Fig. 1 is the associated region of rs2735591.
The left side longitudinal axis is shown as the P value of SNP, and the right side longitudinal axis is shown as recombination fraction, and transverse axis shows its physical location, and the SNP shown in the trilateral is rs2735591.The estimation of recombination fraction is based on China in thousand human genomes and Japanese population sample.Among the figure gene of note come from (
Http:// genome.ucsc.edu/).
Fig. 2 is the relative expression quantity of BCL10 in disease damage tissue and healthy tissues.
Embodiment
Following embodiment is convenient to understand better the present invention, but does not limit the present invention.Experimental technique among the following embodiment if no special instructions, is ordinary method.
Used material, reagent etc. if no special instructions, all can obtain from commercial channels among the following embodiment.
Embodiment 1, rs2735591 are the single nucleotide polymorphism relevant with leprosy
Contriver place research group adopted genome-wide association study (GWAS) to find 7 tumor susceptibility genes (CCDC122, C13orf31, NOD2 of leprosy in Chinese han population in 2009, TNFSF15, HLA-DR, RIPK2 and LRRK2), wherein 5 genes are set up a signal path (Zhang centered by NOD2, F.R., Huang, W., Chen, S, M., Sun, L.D., Liu, H., Li, Y., Cui, Y., Yan, X.X., Yang, H.T., Yang, R.D.et al. (2009) Genomewide association study of leprosy.N.Engl.J.Med., 361,2609-2618.), behind GWAS, found again 2 vulnerability to leprosy genes (IL23R and RAB32) (Zhang, F. in 2011, Liu, H., Chen, S., Low, H., Sun, L., Cui, Y., Chu, T., Li, Y., Fu, X., Yu, Y.et al. (2011) Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy.Nat.Genet., 43,1247-1251.).The Complex Diseases that leprosy concurs as a plurality of minor genes of a class, 9 susceptibility locis finding at present only are the tips of the iceberg of its tumor susceptibility gene spectrum, and more vulnerability to leprosy gene waits further discovery.
The ethics statement
The approval of Ethics Committee of Dermatology and Venereology research institution of Shandong Academy of Medical Sciences has been passed through in this research, and all lepers and normal control have all signed Informed Consent Form.
Research object
From three independent samples of Chinese han population, have 3148 lepers in these three independent samples, 7843 normal controls.They are the independent individual of consanguinity-less relation.The information exchanges such as clinical classification, family history situation and age of onset are crossed the case history collection.Sample standard deviation is by the Quality Control of sample.All lepers and normal control are all from north of China, and age, sex and native place all are complementary.Leper's diagnosis is made a definite diagnosis (clinical foundation comprises claw hand, reel foot and pathology foundation etc.) simultaneously by two experts of Dermatology Department at least.The normal control all personally discusses the disease medical history without leprosy family history and other.
Independent sample 1 is comprised of 706 leper's cases and 514 normal controls; Independent sample 2(verifies sample 1) totally 1504 lepers and 1502 normal controls; Independent sample 3(verifies sample 2) totally 938 lepers and 5827 normal controls.
Wherein, leprosy in China patient's Case definition be meet in following 4 more than 2 or 2, or meet the 3rd person and establish diagnosis: 1, skin decreases with sensory disturbance and closes sweat, or numb district is arranged; 2, peripheral nerve is got involved, and shows as the thick companion's corresponding function of nerve trunk obstacle; 3, skin damage tissue slice or tissue juice smear are found leprosy bacillus; 4, the pathology visible features sexually revises.
Normal control's Case definition: without leprosy medical history and other transmissible disease medical histories, without other autoimmune disorder medical history and family history.
Table 1 has shown the essential information of checking sample 1 and checking sample 2.
Table 1,2442 leprosy in China patients and 7329 normal controls' basic condition
Data (Zhang, F.R., Huang, the W of the whole-genome association of contriver place seminar former studies report used in the research of fs, Chen, S, M., Sun, L.D., Liu, H., Li, Y., Cui, Y., Yan, X.X., Yang, H.T., Yang, R.D.et al. (2009) Genomewide association study of leprosy.N.Engl.J.Med., 361,2609-2618), these data are from independent sample 1; Subordinate phase is checking, another independent sample (checking sample 1) totally 1504 lepers and 1502 normal controls have been used, phase III is further checking, has used the 3rd independent sample (checking sample 2) totally 938 lepers and 5827 normal controls.
The selection of candidate gene and SNP
Log in (http://genome.ucsc.edu/), input " TOLL, CARD " keyword, search altogether from 37 genes of TOLL family and from 53 genes of CARD family, after removing repeat region, have 69 candidate genes and be selected, select the 20KB distance in each expansion of upstream and downstream of each candidate gene.Fs is delivered Zhang, F.R., Huang in earlier stage in contriver place seminar, W., Chen, S, M., Sun, L.D., Liu, H., Li, Y., Cui, Y., Yan, X.X., Yang, H.T., Yang, R.D.et al. (2009) Genomewide association study of leprosy.N.Engl.J.Med., 361, in the GWAS data of 2609-2618, select the related locus that is positioned at above zone in the data results from the past GWAS sample (comprising 1220 samples, 706 leper's cases and 514 normal controls) research of independent sample 1(, in these two GWAS databases, 4363 SNPs that always have 69 candidate genes are analyzed.Differentiate the SNPs:a that can point out relevant evidence by following standard) in expansion GWAS analyzed, the cognation of P value was less than 1.0 * 10
-2B) GWAS first time in 706 routine cases and 514 routine coupling contrasts analyzes, and in the expansion GWAS analysis to 706 routine cases and 5581 routine crowds' contrasts, the cognation of P value makes moderate progress and (reduces at least 10
-1).Amount to, 8 prompting SNPs candidate genes in 2 Toll sample acceptors (ZCCHC11 and FREM1) and 6 CARD genes (BCL10, KCNQ1, MAP2K1, CARD14, NOD1 and VISA) are identified, and are used for further check analysis.
In the check analysis first time of subordinate phase, have among the SNPs that 8 are picked out 6 in 1504 routine Cases of Leprosies of checking sample 1 and 1502 normal controls by the gene type success, yet two other SNPs is in test design or failures in gene type assay.The cognation of 6 SNPs the results are shown in Table 2.In these 6 SNPs, express efficient association (after having proofreaied and correct 6 SNP, p＜0.005) for 2: rs2735591 (P=2.18 * 10
-6, OR=1.32) and rs4889841 (P=6.94 * 10
-4, OR=1.20).In the check analysis second time (phase III), these two SNPs are the further assignment of genes gene mapping of quilt in 938 routine leper's cases of verifying sample 2 and 5827 routine normal controls.Rs2735591 demonstrates effective cognation (P=4.58 * 10 in secondary checking sample
-3, OR=1.17), but rs4889841 does not demonstrate efficient association (P=4.75 * 10 in the past
-2, OR=0.89) (table 3).Rs2735591 demonstrates consistent dependency in two individual authentications and the GWAS sample of having issued, but without heredity heterogeneous (p〉0.05) (table 3).There are height cognation (P=1.27 * 10 in the rs2375591 zone in the sample of having verified
-7, OR=1.27), though in rear 4363 sites of correction in present research the checking (Pcorrected=5.54 * 10
-4) and all surpassing full genomic data (P=1.03 * 10 in the sample (associating GWAS and individual authentication sample)
-9, OR=1.24), comprised altogether 3148 leper's cases and 7843 control (normal control) (table 3).
6 SNP of the relevant property of table 2.
A: less important/main allelotrope
Less important gene frequency in the b:GWAS contrast
C: data from Zhang, F.R., Huang, W., Chen, S, M., Sun, L.D., Liu, H., Li, Y., Cui, Y., Yan, X.X., Yang, H.T., Yang, R.D.et al. (2009) Genomewide association study of leprosy.N.Engl.J.Med., 361,2609-2618.
D: data from Zhang, F., Liu, H., Chen, S., Low, H., Sun, L., Cui, Y., Chu, T., Li, Y., Fu, X., Yu, Y.et al. (2011) Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy.Nat.Genet., 43,1247-1251.
Table 3, the rs2735591 association analysis result in leper and normal control
A: data from Zhang, F.R., Huang, W., Chen, S, M., Sun, L.D., Liu, H., Li, Y., Cui, Y., Yan, X.X., Yang, H.T., Yang, R.D.et al. (2009) Genomewide association study of leprosy.A.Engl.J.Med., 361,2609-2618.
B: all samples that comprise checking sample 1 and checking sample 2.
C: three independent samples that comprise checking sample 1, checking sample 2 and GWAS sample.
Wherein, the method for gene type is as follows:
8 SNPs adopt Sequenom MassArray (San Diego, USA) platform validation, and each sample is used 15ngDNA approximately.At first extract the genomic dna of peripheral blood, after the stdn, sample DNA increases through multi-PRC reaction and comprises the genomic DNA fragment in SNP site, and amplified production carries out the extension of the single chain of SNP locus specificity, and the extension products desalination is also transferred on the chip in 384 holes.Mass spectrograph (MALDI-TOF MS) carries out allelic detection, adopts Sequenom MassARRAY somatotype software that detected result is analyzed.Each checking sample is removed the SNP of callrate＜95%, less important gene frequency＜0.01 or in contrast according to law of genetic equilibrium P＜0.01.
1, whole blood sample collection
In informed consent, and gather research object peripheric venous blood 5ml in the situation of signature written consent book, be positioned over EDTANa
2In the anticoagulant tube, putting-80 ℃ of refrigerator-freezers stores for future use.
2, the DNA concentration standard comprises the steps:
1) utilizes every a standardized sample DNA concentration and the OD ratio (A260/A280, A260/A230) of needing of NanoDrop-1000 concentration tester Accurate Determining.
2) set up electrical form, the DNA numbering that each sample aperture that is ranked need to add.
Carry out the sample of Sequenom MassArray somatotype, leave blank and repeated sample contrast at per 96 orifice plates.
3) according to the order of electrical form, add the DNA that has measured concentration.
Requiring experimental concentration for the sample that carries out Sequenom MassArray somatotype is 12-30ng/ μ l, generally take 18ng/ μ l as good.And A260/A280 ratio between 1.5-2.0, A260/230 is between 1.5-2.3, be higher than 18ng/ul such as DNA concentration and then add an amount of FG3, with the concentration mark to 18ng/ul; Be lower than 12ng/ul such as DNA concentration, then again extract qualified DNA from blood.Concentration directly adds between 12-18ng/ μ l.
Stick the viscosity masking foil after centrifugal, and put on the information such as sample plane label, sample type, source place with marker pen.
4) on dull and stereotyped whizzer, centrifugal 3 minutes of 3000g, deposit in-20 ℃ for subsequent use.
3, multiplex PCR
Wherein, amplification comprises that the primer of genomic DNA fragment of rs2735591 is as follows in the multiplex PCR:
Sequence 1 in the ACGTTGGATGCTCATCCTACTTCCCTGTTT(sequence table) and
4, the extension of the single chain of SNP locus specificity
Wherein, extend primer according to upstream, SNP site in the human genome (not comprising this SNP site) design, front 1 Nucleotide in last 1 Nucleotide correspondence of described extension primer this SNP site in human genome.The sequence of the extension primer of rs2735591 is the sequence 3 in the TCCCTGTTTTATTTTTTCCTCTTAG(sequence table).
5, data quality control
1) call rate calculating is carried out in the SNP of somatotype, remove call rate＜90% SNP or SNPs of gene frequency＜0.01;
2) SNP is carried out genetic equilibrium check, remove the P of Hardy-Weinberg balance check in the SNP(check sample that departs from the law of genetic equilibrium＜=0.001);
3) in Sequenom MassArray system, check the somatotype dendrogram of SNP, remove dendrogram and divide heap unclear SNP.
4) sample Quality Control: the sample of directly removing the somatotype failure.
To carry out statistical study by sample and the SNP of Quality Control.
6, data statistic analysis
Utilize Plink 1.07 softwares that somatotype success and the SNP by Quality Control are done the gene phenotype correlation analysis in case group and control group, in two individual authentication samples (checking sample 1 and checking sample 2), genotype one phenotype association study adopts Cochran-Armitage trend-monitoring.In associating sample (independent sample 1+ checking sample 1+ checking sample 2), adopt Cochran – Mantel – Haenszel to detect.Multiple logistic regression analysis is for detection of the independence of the signal in the zone.Inspection level α take 0.05 divided by the SNP number by quality control as inspection level.The Q check has been considered as remarkable genetic heterogeneity to P value after the SNP correct detection less than 0.05 for assessment of the significance of genetic heterogeneity.
The genotype of rs2735591 and phenotype association study result are as shown in table 4, show that rs2735591 is the single nucleotide polymorphism relevant with leprosy.
Genotype and the phenotype association study result of table 4.rs2735591
By the association study in three groups of independent samples, determine that rs2735591 is the single nucleotide polymorphism relevant with leprosy, it is apart from BLC10(B cell lymphoma/leukemia-10) gene 2Kb.Rs2735591 is present in the linkage disequilibrium zone of the upper about 400kb size of 1p22, and this zone has BCL10 and other a few gene and transcriptons simultaneously.Except BCL10, also have other several tumor susceptibility genes at this desmic region.C1orf52 adjoins mutually with DDAH1 and BCL10.The enzyme that the DDAH1 coding is synthetic relevant with nitrogen protoxide, C1orf52 may be the gene that does not have function.
For whether checking BLC10 gene is the potential master regulation gene of transcriptional expression, rs2735591 is carried out eQTL analyze, from the wax stone resources bank that Pathology Deparment of Shandong Dermatopathy Cypridopathy Prevention and Cure Institute preserves, choose leprosy sample 36 examples of making a definite diagnosis.Normal control sample 32 examples are taken from the normal skin at Shandong Dermatopathy Cypridopathy Prevention and Cure Institute surgical resection sample edge, confirm as normal skin through histopathology.Above sample is all fixed-paraffin embedding through formalin.Adopt the method for Branched-chain DNA, by fluorescent probe mRNA is hybridized, and then detect and determine the expression amount of BCL10 gene in tissue through the fluorescent signal of three grades of amplifications, wherein use house-keeping gene PPIB gene (GenBank Accession Number NM_000942) and HPRT1 gene (NM_000194) to carry out relative expression's component analysis as the internal reference gene.Use SPSS13.0 software and carry out the statistical procedures experimental data.The result shows that the expression amount of BCL10 is starkly lower than healthy tissues (P=0.0007) (Fig. 2 and table 5) in the disease damage tissue.
Table 5, BCL10 gene are in the comparison (means standard deviation) of leprosy sample and normal control sample expression amount
Consistent with the result of association analysis.Confirm that BCL10 is a kind of new vulnerability to leprosy gene, also emphasized the vital role of intrinsic in leprosy and adaptive immune response simultaneously.
The albumen of BCL10 coding belongs to CARD family, play an important role in the NF-KB path, and NF-KB plays an important role in the infection of leprosy bacillus.BCL10 works by CARMA1-Bcl10-MALT1 and CARD9-Bcl10-MALT1 respectively in lymphoidocyte L-CBM and marrow like cell M-CBM.As the immune factor of inherence, the M-CBM complex body acts on the immunity receptor (ITAM) of NF-γ B.M-CBM can also regulate the acceptor (TLRs) of MAPKs, and regulates the NOD2 path by RIP2.L-CBM participates in regulating adaptive immunity, plays an important role in NF-γ B path, comprises T cell and B cell signal path.The TLR4 that L-CBM may relate to NF-γ B in the B cell regulates.Except the NOD2 path, the BCL10 that this research is found plays an important role in the morbidity of leprosy.
Claims (10)
1. the polymorphism of rs2735591 or the genotypic material application in the product of the preparation detection single nucleotide polymorphism relevant with leprosy in the detection human genome.
2. the polymorphism of rs2735591 or the genotypic material application in the product of characterization or the assistant identification single nucleotide polymorphism relevant with leprosy in the detection human genome.
3. the polymorphism of rs2735591 or the genotypic material application in preparation examination leper product in the detection human genome.
4. the polymorphism of rs2735591 or the genotypic material application in preparation detection leprosy susceptibility product in the detection human genome.
5. the application of the single nucleotide polymorphism in the human genome in the product of preparation detection leprosy tumor susceptibility gene, it is characterized in that: described single nucleotide polymorphism is that refSNP ID is the dna sequence polymorphism of rs2735591.
6. the application of the single nucleotide polymorphism in the human genome in the product of characterization or assistant identification leprosy tumor susceptibility gene is characterized in that: described single nucleotide polymorphism is that refSNP ID is the dna sequence polymorphism of rs2735591.
7. the application of the polymorphism of rs2735591 in preparation examination leper product in the human genome.
8. the application of the polymorphism of rs2735591 in preparation detection leprosy susceptibility product in the human genome.
9. contain the product that detects the material of rs2735591 polymorphism in the human genome, be any product in a)-d):
The product of the single nucleotide polymorphism that a) detection is relevant with leprosy;
The product of the single nucleotide polymorphism that b) evaluation or assistant identification are relevant with leprosy;
C) examination leper product;
D) detect leprosy susceptibility product.
10. product according to claim 9 is characterized in that: the material of the polymorphism of rs2735591 contains PCR primer and the single-basic extension primer that amplification comprises the genomic DNA fragment of rs2735591 in the described detection human genome.
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| CN104293947A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs58600253 in detection of leprosy susceptibility genes |
| CN104293949A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs73058713 in detecting lepriasis predisposing gene |
| CN104293948A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs2221593 in detecting leprosy susceptibility genes |
| CN104293950A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs77061563 in detecting leprosy susceptibility genes |
| CN104293946A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs663743 in detection of lepriasis susceptibility gene |
| CN104293952A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs10817758 in detection of a lepriasis susceptibility gene |
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| CN104293947A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs58600253 in detection of leprosy susceptibility genes |
| CN104293949A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs73058713 in detecting lepriasis predisposing gene |
| CN104293948A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs2221593 in detecting leprosy susceptibility genes |
| CN104293950A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs77061563 in detecting leprosy susceptibility genes |
| CN104293946A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs663743 in detection of lepriasis susceptibility gene |
| CN104293952A (en) * | 2014-10-10 | 2015-01-21 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs10817758 in detection of a lepriasis susceptibility gene |
| CN104293949B (en) * | 2014-10-10 | 2016-03-23 | 山东省皮肤病性病防治研究所 | Single nucleotide polymorphism rs73058713 is detecting the application in susceptibility gene of leprosy |
| CN104293947B (en) * | 2014-10-10 | 2016-03-23 | 山东省皮肤病性病防治研究所 | Single nucleotide polymorphism rs58600253 is detecting the application in susceptibility gene of leprosy |
| CN104293950B (en) * | 2014-10-10 | 2016-03-23 | 山东省皮肤病性病防治研究所 | Single nucleotide polymorphism rs77061563 is detecting the application in susceptibility gene of leprosy |
| CN104293946B (en) * | 2014-10-10 | 2016-03-23 | 山东省皮肤病性病防治研究所 | Single nucleotide polymorphism rs663743 is detecting the application in susceptibility gene of leprosy |
| CN104293948B (en) * | 2014-10-10 | 2016-03-23 | 山东省皮肤病性病防治研究所 | Single nucleotide polymorphism rs2221593 is detecting the application in susceptibility gene of leprosy |
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